Acute inflammation is a predisposing factor for weight gain and insulin resistance

ABSTRACT Aim Intense endotoxaemia and infection are able to reduce appetite and induce a catabolic state, therefore leading to weight loss. However, it is underexplored its late effects on energy homeostasis, regulation of body weight and glucose metabolism. Here we addressed whether serial intense endotoxaemia, characterized by an acute phase response and weight loss, could be an aggravating or predisposing factor to diet-induced obesity (DIO) and associated metabolic impairments. Methods Male Swiss Webster mice were submitted to 8 consecutive doses of lipopolysaccharide (LPS - 10 mg/kg), followed by 10 weeks in high-fat diet (HFD). Results After the end of the acute endotoxaemia period, mice under chow diet recovered their weight rapidly, within one-week recovery period, which remained similar to its control counterparts. However, acute endotoxaemia caused a long-lasting adipose tissue expression of the inflammatory markers TLR-4, CD14 and serum amyloid A (SAA) and, when challenged by a HFD, LPS-treated mice gained more weight, showed increased fat depots, leptin and insulin levels, and also impaired insulin sensitivity. Conclusions LPS-treated mice showed a higher susceptibility to the harmful effects of a subsequent HFD. Conditions leading to intense and recurrent endotoxaemia, such as common childhood bacterial infections, may resound for a long time and aggravate the effects of a western diet. If confirmed in humans, infections should be considered an additional factor contributing to obesity and type 2 diabetes epidemics and additionally impose more rigorous dietary recommendations for patients in post-infection recovery. Bullet points Intense endotoxemia causes a long-lasting increase in the expression of inflammatory markers in adipose tissue. Intense endotoxemia is a predisposing factor to diet-induced obesity and insulin resistance. Infections may contribute to weight gain when associated to a western diet.